The objective of the proposed research will be to prepare light and electron microscope (EM) autoradiographs of radiolabeled insulin and cholecystokinin in the isolated perfused rat pancreas. The hormones will be injected into the arterial supply of the pancreas, followed at various times by perfusion-fixation of the pancreatic tissue with glutaraldehyde-paraformaldehyde. A similar approach has been proven successful for preparing both light and EM autoradiographs of labeled insulin in the perfused rat liver. We plan to determine which cells of the pancreas have hormone receptors (acinar, ductal and connective), which portion of the cells (basal, apical or lateral) have these receptors, whether the hormones are internalized, and, if internalized, on what intracellular organelles do they locate. These studies should provide data concerning hormonal regulation and interaction in the exocrine pancreas, and yield an improved understanding of pancreatic diseases with abnormal secretion, such as cystic fibrosis.